(Reuters Health) - Despite warnings that supplemental testosterone may raise the risk of stroke and heart attack, doctors continue to prescribe the hormone off-label to men with cardiovascular disease, a U.S. study finds.
After poring over 10 years of prescription data, researchers found that men with heart disease were no less likely than those without it to receive a testosterone prescription despite warnings from the Food and Drug Administration (FDA) in 2014 that the hormone might increase cardiovascular risk, researchers reported in JAMA Internal Medicine.
“Safety concerns began emerging in 2010,” said lead author Dr. Nancy Mordon of the Dartmouth Institute of Health Policy and Clinical Practice in Lebanon, New Hampshire. “We looked specifically at heart disease patients compared to those with no heart disease trying to find out if we were being careful with patients who are at the highest risk. It turned out that patients were more likely to get testosterone if they had heart disease.”
One of the biggest problems is that testosterone hasn’t been shown to have significant benefits, Mordon said. “Physicians are part of the equation,” she added. “They are prescribing products in a gray zone where efficacy and safety are unclear and they are prescribing to a population at risk. The bottom line is that physicians should be having in-depth discussion with their patients.”
A trial that looked at the impact of testosterone supplementation on sexual function “showed a tiny benefit, 0.2 points on a 13 point scale,” Mordon said.
For the new analysis, Mordon and colleagues examined a large random sample of Medicare fee-for-service data collected between January 1, 2007 and December 31, 2016. They looked separately at testosterone prescriptions for approved conditions and those that were off-label, meaning prescribed to treat a condition for which the drug has not been FDA-approved.
The annual number of patients studied ranged from 1.8 million to 3.1 million, representing 10 to 20 percent of fee-for-service male Medicare enrollees older than 50. The researchers found that testosterone use was consistently higher for men with heart disease compared to those without it.
Dr. Harry Fisch, who wasn’t involved in the study, was not surprised. First of all, he said, men with cardiovascular disease tend to have lower testosterone levels. In addition, people with heart disease are often overweight and “people who are heavier tend to have lower testosterone,” said Fisch, a clinical professor of urology and reproductive medicine at Weill Cornell Medical College in New York City. “The bigger the belly, the lower the testosterone.”
A better solution for these men would be “diet and exercise,” said Fisch. “That will lower the belly fat.”
Fisch said he never prescribes testosterone off-label for low hormone levels. Beyond safety issues, “there is not a study showing what symptoms are improved with testosterone,” Fisch said.
A large, ongoing randomized trial - the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men - should be completed in 2022, said Dr. Erin Michos of the Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins School of Medicine in Baltimore, Maryland. “The results of that trial could be the tipping point that changes practice patterns.”
Low testosterone “may be a marker of a poorer health state, so it’s not surprising that many men with coronary artery disease have low testosterone,” said Michos, who wasn’t involved in the current study. “Men with diabetes and (coronary artery disease) frequently have vascular erectile dysfunction, stemming from atherosclerosis and endothelial dysfunction. Blaming low testosterone levels may seem like an easy solution when actually the problem stems from a more complicated underlying vascular disorder,” she said in an email.
“Additionally,” Michos said, “there might be a tendency to blame a lot of nonspecific symptoms such as fatigue or lack of fitness on the low testosterone level whereas there might be other modifiable etiologies for those symptoms, such as obesity and sedentary behavior.”
SOURCE: bit.ly/2ESGGAX JAMA Internal Medicine, online December 28, 2018.